DNA methyltransferase family (DNMT)

The DNA methyltransferase (DNMT) family comprises enzymes responsible for the covalent addition of a methyl group to the C5 position of cytosine, a key epigenetic modification that regulates gene expression and genomic stability [UniProt: P26358]. The family includes DNMT1, which functions as a maintenance methyltransferase during DNA replication, and DNMT3A and DNMT3B, which are responsible for de novo methylation during development [PubMed: 22429544]. Dysregulation of these enzymes, often leading to the silencing of tumor suppressor genes through promoter hypermethylation, is a hallmark of various cancers, including myelodysplastic syndromes and acute myeloid leukemia [PubMed: 24513165]. Therapeutic targeting of DNMTs primarily utilizes hypomethylating agents such as azacitidine and decitabine, which are nucleoside analogs that trap the enzymes on DNA, leading to their proteasomal degradation [PubMed: 20157222]. This depletion results in global DNA demethylation and the restoration of normal gene expression patterns, although it is often accompanied by side effects like myelosuppression [StatPearls: NBK537112]. Beyond oncology, DNMTs are implicated in neurodevelopmental and autoimmune disorders, making them versatile targets for epigenetic therapy [PubMed: 29211676].

Other names

DNA (cytosine-5)-methyltransferaseC-5 cytosine-specific DNA methylaseDNA methylaseDNMT1DNMT3ADNMT3BDNMT3L

DNMT inhibitors, primarily nucleoside analogs, incorporate into DNA during replication and form a covalent bond with the enzyme, leading to its depletion and subsequent DNA hypomethylation [PubMed: 20157222].